Celastrol Ameliorates Neuronal Mitochondrial Dysfunction Induced by Intracerebral Hemorrhage via Targeting cAMP-Activated Exchange Protein-1.

Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, the primary active component of Tripterygium wilfordii, is a natural product that exhibits mitochondrial and neuronal protection in various cell types. This study aims to investigate the neuroprotective effects of celastrol against ICH-induced SBI and explore its underlying mechanisms. Celastrol improves neurobehavioral and cognitive abilities in mice with autologous blood-induced ICH, reduces neuronal death in vivo and in vitro, and promotes mitochondrial function recovery in neurons. Single-cell nuclear sequencing reveals that the cyclic adenosine monophosphate (cAMP)/cAMP-activated exchange protein-1 (EPAC-1) signaling pathways are impacted by celastrol. Celastrol binds to cNMP (a domain of EPAC-1) to inhibit its interaction with voltage-dependent anion-selective channel protein 1 (VDAC1) and blocks the opening of mitochondrial permeability transition pores. After neuron-specific knockout of EPAC1, the neuroprotective effects of celastrol are diminished. In summary, this study demonstrates that celastrol, through its interaction with EPAC-1, ameliorates mitochondrial dysfunction in neurons, thus potentially improving SBI induced by ICH. These findings suggest that targeting EPAC-1 with celastrol can be a promising therapeutic approach for treating ICH-induced SBI.

Risk Factors for External Ventricular Drainage-Related Infection: A Systematic Review and Meta-analysis.

Background and Objectives: External ventricular drainage (EVD) is one of the most commonly performed neurosurgical procedures, but EVD-related infection constitutes a significant health concern. Yet, little consensus identifies the risk factors for the development of EVD-related infection. Therefore, we performed a meta-analysis to systematically summarize existing evidence on the incidence and risk factors for EVD-related infection. Methods: PubMed, Embase, and the Cochrane Library databases from database inception to February 28, 2022, were searched for all studies investigating the incidence and risk factors for EVD-related infection. Data were assessed by R-4.2.0 software. The meta-analysis was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 48 studies were included. Among the 29 factors analyzed, statistically significant risk factors were subarachnoid hemorrhage(SAH)/intraventricular hemorrhage(IVH) (OR = 1.48, 95% CI = 1.20-1.82, p < 0.001), concomitant systemic infection (OR = 1.90, 95% CI = 1.34-2.70, p < 0.001), other neurosurgical procedures (OR = 1.76, 95% CI = 1.02-3.04, p = 0.041), change of catheter (OR = 5.05, 95% CI = 3.67-6.96, p < 0.001), bilateral EVDs (OR = 2.25, 95% CI = 1.03-4.89, p = 0.041), (cerebrospinal fluid) CSF leak (OR = 3.19, 95% CI = 2.12-4.81, p < 0.001) and duration of EVD >7 days (OR = 4.62, 95% CI = 2.26-9.43, p < 0.001). The use of silver-coated catheters (OR = 0.57, 95% CI = 0.38-0.87, p = 0.008) and antibiotic-impregnated catheters (OR = 0.60, 95% CI = 0.41-0.88, p = 0.009) might help reduce the risk of infection. No significant difference was indicated in studies evaluating factors like diabetes mellitus (OR = 1.25, 95% CI = 0.90-1.75, p = 0.178), steroids used (OR = 1.52, 95% CI = 0.96-2.4, p = 0.074), prophylactic antibiotics(OR = 0.87, 95% CI = 0.66-1.14, p = 0.308). Discussion: The meta-analysis of various relevant factors in the onset of EVD-related infection in patients submitted to EVD enabled us to establish a more probable profile of the patients who are more likely to develop it during the treatment.

Flexible Capacitive Sensing and Ultrasound Calibration for Skeletal Muscle Deformations.

Skeletal muscles are critical to human-limb motion dynamics and energetics, where their mechanical states are seldom explored in vitro due to practical limitations of sensing technologies. This article aims to capture mechanical deformations of muscle contraction using wearable flexible sensors, which is justified with model calibration and experimental validation. The capacitive sensor is designed with the composite of conductive fabric electrodes and the porous dielectric layer to increase the pressure sensitivity and prevent lateral expansions. In this way, the compressive displacement of muscle deformation is captured in the muscle-sensor coupling model in terms of sensor deformation and parameters of pretension, material, and shape properties. The sensing model is calibrated in a linear form using ultrasound medical imaging. The sensor is capable of measuring muscle strain of 70% with an error of <3.6% and temperature disturbance of <5.6%. After 10K cycles of compression, the drift is only 3.3%. Immediate application of the proposed method is illustrated by gait pattern identification, where the K-nearest neighbor prediction accuracy of squats, level walking, stair ascent/descent, and ramp ascent is over 97% with a standard deviation below 2.6% compared to that of 94.61 ± 4.24% for ramp descent, and the response time is 14.37 ± 0.52 ms. The wearable sensing method is valid for muscle deformation monitoring and gait pattern identification, and it provides an alternative approach to capture mechanical motions of muscles, which is anticipated to contribute to understand locomotion biomechanics in terms of muscle forces and metabolic landscapes.

Decorating Calcium-Based Materials with Transition Metal Elements for Directly Capturing and Storing Solar Energy.

Direct solar-driven thermochemical energy storage system puts forward new requirements for calcium-based materials with high optical absorption, high capacity of energy storage density, high cycling stability, and low costs. In this work, the novelty relies on the fact that calcium-based composites modified by transition metal elements can directly capture solar energy for storing. Meanwhile, this work provides the design criteria of calcium-based materials with high optical absorption in theory and screens appropriate decorating elements to modify CaCO3 for satisfying multiple demands in experiments. The design criteria for promoting light absorption of calcium-based materials were established by electromagnetic theory while the dark transition metal elements (Cr, Mn, Fe, Co, Ni, and Cu) were doped in binary combination to experimentally modify calcium-based composites through the sol-gel method. The results indicate that calcium-based materials with porous structure (doped with Mn element) not only have high optical absorption (>75%) but also possess high cycling stability (attenuation <9% after 20 cycles) and high capacity of energy storage density (>1260 kJ/kg). After comprehensive consideration of optical absorption, cycling stability, capacity of energy storage density, and economic cost, the samples of Ca-Mn-Fe = 100-2-4 and Ca-Cr-Mn = 100-2-4 stand out to be the most promising candidates for large-scale application of thermochemical energy storage. This work provides novel promising calcium-based materials for direct solar-driven thermochemical energy storage system to realize high-efficiency solar thermal conversion.

Scalp block for postoperative pain after craniotomy: A meta-analysis of randomized control trials.

Background: Postoperative pain after craniotomy is an important clinical concern because it might lead to brain hyperemia and elevated intracranial pressure. Considering the side effects of opioid, several studies have been conducted to investigate the effect of local anesthetics, especially the scalp block, on postoperative pain. However, the strength of evidence supporting this practice for postoperative pain after craniotomy was unclear and the best occasion of scalp block was also not identified. Therefore, we conducted a meta-analysis to evaluate the efficacy, safety, and the best occasion of scalp block for postoperative pain after craniotomy. Methods: PubMed, Embase, and the Cochrane Library databases from database inception to October 10, 2021 were searched for all randomized controlled trials evaluating the effect of scalp block on postoperative pain after craniotomy. Data were assessed by StataMP 16 software. Results: A total of 12 studies were included. A random-effect model was used to analyze all data. Patients under scalp block earned fewer scores than the non-scalp block group in visual analogue scale at the very early period (MD = -1.97, 95% CI = -3.07 to -0.88), early period (MD = -1.84, 95% CI = -2.95 to -0.73) and intermediate period (MD = -1.16, 95% CI = -1.84 to -0.49). Scalp block could also significantly prolong the time of the first request of rescue analgesia and reduce the use of additional analgesics without a significant difference in the incidence of complications. Subgroup analysis showed there was no significant difference in analgesia effect between pre-incision scalp block and post-incision scalp block in all periods. Conclusion: Scalp block could lead to lower pain intensity scores, more time of the first request of rescue analgesia, and fewer analgesic drugs applied in the first 12 h after craniotomy. There was no significant difference between pre-incision and post-incision scalp block in the occurrence and severity of postoperative pain.

Real-time threshold determination of auditory brainstem responses by cross-correlation analysis.

Auditory brainstem response (ABR) serves as an objective indication of auditory perception at a given sound level and is nowadays widely used in hearing function assessment. Despite efforts for automation over decades, ABR threshold determination by machine algorithms remains unreliable and thereby one still relies on visual identification by trained personnel. Here, we described a procedure for automatic threshold determination that can be used in both animal and human ABR tests. The method terminates level averaging of ABR recordings upon detection of time-locked waveform through cross-correlation analysis. The threshold level was then indicated by a dramatic increase in the sweep numbers required to produce "qualified" level averaging. A good match was obtained between the algorithm outcome and the human readouts. Moreover, the method varies the level averaging based on the cross-correlation, thereby adapting to the signal-to-noise ratio of sweep recordings. These features empower a robust and fully automated ABR test.

Inhibition of mouse RM-1 prostate cancer and B16F10 melanoma by the fusion protein of HSP65 & STEAP1 186-193.

The research of tumor vaccine plays a crucial role in tumor immunotherapy. This study has constructed and prepared a fusion protein vaccine of heat shock protein 65 (HSP65) and the octapeptide epitope 186-193 of the six transmembrane epithelial antigen of the prostate 1 (STEAP1 186-193), and investigated the inhibitory effect of the fusion protein on mouse RM-1 prostate cancer and B16F10 melanoma xenografts. The fusion protein His-HSP65-STEAP1 186-193 (HHST1), His-HSP65-2×STEAP1 186-193 (HHST2) and His-HSP65-6×STEAP1 186-193 (HHST6) were obtained by setting different copy number of STEAP1 186-193 and adding His purification tag before HSP65. Firstly the inhibitory effect of fusion protein on mouse RM-1 prostate cancer xenografts has been studied, which could be the basis of the study the inhibitory effect of the best fusion protein on mouse B16F10 melanoma xenografts. All studies compared with the fusion protein His-HSP65 (HHSP65), the fusion proteins HHST1, HHST2 and HHST6 all could significantly inhibit the growth of mouse RM-1 prostate cancer xenografts. In addition, the fusion protein HHST2 was proved to be the best compared with the fusion proteins HHST1 and HHST6 (P<0.05). Apart from this, compared with the fusion protein HHSP65, the fusion protein HHST2 also significantly inhibited the growth of mouse beared B16F10 melanoma. The results above indicate that HSP65 and STEAP1 186-193 can significantly inhibit the growth of mouse RM-1 prostate cancer and B16F10 melanoma xenografts, and the appropriate increase of copy number can effectively improve that the fusion protein has an excellent anti-tumor ability.